This is a multi-center, randomized, Phase 2/3 study to evaluate the safety and efficacy of pyronaridine-artesunate in participants with corona virus disease 2019 (COVID-19). Pyronaridine-artesunate has been approved in Europe, Asia and Africa under brand name of Pyramax® or Artecom® as a treatment for malaria. The study will be conducted in two stages: open-label (Stage 1) and double-blind (Stage 2). Up to approximately 402 participants (20 participants in Stage 1 and 382 participants in Stage 2) are planned to be enrolled in the study and will be randomized to receive either Artecom® or matching placebo at a ratio of 1:1 in Stage 2. The dose of Artecom® will be determined by the participant's body weight, according to previously established guidelines. An independent Drug Safety Monitoring Board (DSMB) will be established to review the safety at regular intervals during the conduct of the trial. The DSMB will be subject to a Charter and will review after 20 participants have been recruited, and thereafter when 191 participants have been recruited. Ad-hoc DSMB meetings may be held at any time during the study if there are any major safety concerns. A final DSMB will be conducted when all participants have been recruited in the trial.
\<Stage 1\> In Stage 1, the trial will be conducted in 20 participants for 28 days in a single arm, open-label design. Artecom® will be administered orally once a day for 3 consecutive days. All subjects will be evaluated for efficacy and safety for 28 days. After the completion of the final participant in Stage 1, the DSMB will review the safety data from Stage 1 and determine whether to proceed to Stage 2. \<Stage 2\> In Stage 2, a total of 382 participants will be enrolled and randomized in a double blinded manner to receive either Artecom® or placebo (1:1 ratio) orally once a day for 3 consecutive days. All subjects will be evaluated for efficacy and safety for 28 days. A second DSMB meeting and review of all available blinded safety data will occur after 191 participants have completed Day 28. A final DSMB meeting will be held after the completion of a study assessment by the last participant.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
402
\* Participant body weight (Artecom® dose) * ≥ 65kg (Artecom® 4 tablets: Pyronaridine 720mg/ Artesunate 240mg) * ≥ 45kg and \< 65kg (Artecom® 3 tablets: Pyronaridine 540mg/ Artesunate 180mg)
\* Participant body weight (Placebo dose) * ≥ 65kg (Placebo 4 tablets) * ≥ 45kg and \< 65kg (Placebo 3 tablets)
De La Salle University Medical Center
Dasmariñas, Gov, D. Mangubat St, 4114 Cavite, Philippines
RECRUITINGThe Medical City
Pasig, Ortigas Avenue, Barangay Ugong, Metro Manila, Philippines
NOT_YET_RECRUITINGLung Center of the Philippines
Quezon City, Quezon Avenue, Quezon City, 1100 Philippines, Philippines
RECRUITINGPhilippine General Hospital
Manila, Taft Ave, Ermita, Manila, 1000 Metro, Philippines
RECRUITINGProportion of participants with clinical improvement as defined by an improvement of categories on the WHO Ordinal Scale of clinical status until Days 28.
\* WHO Ordinal scale: 0. No clinical or virological evidence of infection 1. No limitation of activities 2. Limitation of activities 3. Hospitalized, no oxygen therapy 4. Oxygen by mask or nasal prongs 5. Non-invasive ventilation or high-flow oxygen 6. Intubation and mechanical ventilation 7. Ventilation + additional organ support - Pressers, Renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO) 8. Death
Time frame: follows up to 28 days
Time to clinical improvement was defined as time from randomization to an improvement of categories on the WHO Ordinal Scale of clinical status.
Clinical improvement within 28 days since start of treatment, defined as a decrease of at least 2 point from baseline of a nine-point WHO ordinal scale.
Time frame: follows up to 28 days
Changes in the WHO Ordinal Scale for Clinical Improvement until Days 28 compared to Baseline.
Compare statistical results of an increase or decrease in a nine-point WHO ordinal scale between two groups.
Time frame: follows up to 28 days
Changes in National Early Warning Score (NEWS) until Days 28 compared to Baseline.
NEWS determines the degree of illness of a patient and promotes critical care intervention. The score range from 0-20, with a higher score representing a higher risk of morbidity. Compare statistical results of an increase or decrease in NEWS between two groups.
Time frame: follows up to 28 days
Proportion of participants with negative for COVID-19 as determined by real-time RT-PCR test until Days 14.
Proportion of subjects who are RT-PCR negative for COVID-19
Time frame: follows up to 14 days
Changes in viral load until Days 14 compared to Baseline.
Viral load reduction of COVID-19 until Days 14 compared to the baseline.
Time frame: follows up to 14 days
The time to body temperature normalization after the administration of investigational Product (IP).
Maintaining underarm ≤36.7 °C, or oral ≤36.9°C, or rectal ≤37.3°C, or eardrum ≤37.2°C, for at least 24 hours without administering fever reducing medication after the administration of IP.
Time frame: follows up to 28 days
The time to respiratory rate normalization after the administration of IP.
Maintain 12/min ≤ respiratory rate ≤ 20/min for at least 24 hours.
Time frame: follows up to 28 days
The time to oxygen saturation (SpO2) normalization after the administration of IP.
SpO2 ≥95% for at least 24 hours.
Time frame: follows up to 28 days
Mortality rate at Day 28.
Compare the mortality rate between two groups.
Time frame: Day 28
Duration of hospitalization (Day 1 to Day 28).
Number of days the subject from the start of treatment to hospital discharge.
Time frame: follows up to 28 days
The incidence of adverse events (AEs).
The incidence rate of adverse events
Time frame: follows up to 28 days
The incidence of serious adverse events (SAEs).
The incidence rate of serious adverse events
Time frame: follows up to 28 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.